Presenilin family is a group of related transmembrane proteins that contain nine transmembrane domains, with a large loop between the sixth and seventh. There are two presenilins in vertebrates, referred to as presenilin-1 (PS-1, encoded by PSEN1 gene in humans) and presenilin-2 (PS-2, encoded by PSEN2 gene in humans). Presenilins constitute the catalytic subunits of the γ-secretases, which are membrane-embedded aspartyl protease complexes responsible for generating the carboxyl terminus of the amyloid β-protein (Aβ) from the amyloid protein precursor (APP). Presenilins were primarily found to be sites of missense mutations responsible for early-onset Alzheimer disease (AD). Presenilins undergo cleavage in an alpha-helical region of one of the cytoplasmic loops to produce a large N-terminal and a smaller C-terminal fragment that together form part of the functional protein.
Mutations in the presenilin genes are considered to account for about 20–25% of all familial AD cases. Presenilins are also suggested to be involved in the modulation of intracellular Ca²⁺ which plays a part in presynaptic neurotransmitter release and long-term potentiation induction. Here, the two members of the presenilin family are covered in further detail for your review.
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